Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease.

Genome sequencing is often pivotal in the diagnosis of rare diseases, but many of these conditions lack specific treatments. We describe how molecular diagnosis of a rare, fatal neurodegenerative condition led to the rational design, testing, and manufacture of milasen, a splice-modulating antisense oligonucleotide drug tailored to a particular patient. Proof-of-concept experiments in cell lines from the patient served as the basis for launching an "N-of-1" study of milasen within 1 year after first contact with the patient. There were no serious adverse events, and treatment was associated with objective reduction in seizures (determined by electroencephalography and parental reporting). This study offers a possible template for the rapid development of patient-customized treatments. (Funded by Mila's Miracle Foundation and others.).

Mechanisms underlying genetic susceptibility to multisystem inflammatory syndrome in children (MIS-C).

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a pediatric complication of severe acute respiratory syndrome coronavirus 2 infection that is characterized by multiorgan inflammation and frequently by cardiovascular dysfunction. It occurs predominantly in otherwise healthy children. We previously reported haploinsufficiency of suppressor of cytokine signaling 1 (SOCS1), a negative regulator of type I and II interferons, as a genetic risk factor for MIS-C. OBJECTIVES: We aimed to identify additional genetic mechanisms underlying susceptibility to severe acute respiratory syndrome coronavirus 2-associated MIS-C. METHODS: In a single-center, prospective cohort study, whole exome sequencing was performed on patients with MIS-C. The impact of candidate variants was tested by using patients' PBMCs obtained at least 7 months after recovery. RESULTS: We enrolled 18 patients with MIS-C (median age = 8 years; interquartile range = 5-12.25 years), of whom 89% had no conditions other than obesity. In 2 boys with no significant infection history, we identified and validated hemizygous deleterious defects in XIAP, encoding X-linked inhibitor of apoptosis, and CYBB, encoding cytochrome b-245, beta subunit. Including the previously reported SOCS1 haploinsufficiency, a genetic diagnosis was identified in 3 of 18 patients (17%). In contrast to patients with mild COVID-19, patients with defects in SOCS1, XIAP, or CYBB exhibit an inflammatory immune cell transcriptome with enrichment of differentially expressed genes in pathways downstream of IL-18, oncostatin M, and nuclear factor κB, even after recovery. CONCLUSIONS: Although inflammatory disorders are rare in the general population, our cohort of patients with MIS-C was enriched for monogenic susceptibility to inflammation. Our results support the use of next-generation sequencing in previously healthy children who develop MIS-C.

Determining factors that influence parents' perceptions of telehealth provided in a pediatric gastroenterological practice: A quality improvement project.

BACKGROUND: In response to the COVID-19 pandemic, local and institutional guidelines restricted non-emergent, in-person visits in outpatient specialty clinics. Nurse practitioners (NPs) in pediatric gastroenterology clinics immediately shifted their practice to telehealth (TH). LOCAL PROBLEM: The shift to TH necessitated a change in practice. This quality improvement project was designed to define factors influencing family's perceptions of TH and secure feedback on the TH experience. TH is remaining an option for accessing care even as restrictions are being lifted. Feedback is necessary to ensure that quality of care and high patient satisfaction are maintained in a virtual environment. METHODS: The Unified Theory of Acceptance and Use of Technology was used to frame the project. Surveys were collected from NPs related to services provided and complexities of each encounter. Post-visit surveys were conducted with families to assess their perceptions of the visit. Findings were discussed to identify and address gaps in service. RESULTS: Parent/family surveys were consistent with NP feedback. Results indicated that parents were satisfied with care provided via TH, but that these visits were limited by incomplete assessments, lacked the intimacy of in-person encounters and were often difficult to access due to technological issues. CONCLUSIONS: It is anticipated that TH will be used in the post pandemic era to provide routine and non-emergent acute care. Institutions and providers need to consider factors influencing the patient experience learned during the pandemic and implement evidenced-based strategies that ensure quality care that meets patients' needs.

Addressing Bullying and Lateral Violence in the Workplace: A Quality Improvement Initiative.

BACKGROUND: Bullying and lateral violence are pervasive in the nursing workforce and have profound psychosocial, physical, safety, and financial consequences for nurses, their patients, and the overall health care organization. PROBLEM: Unit-based nursing leaders may be aware of bullying and lateral violence but be unsure of the best approaches to address it. APPROACH: An iterative, multimodal quality improvement initiative was crafted on the basis of the available evidence and principles of transformational, adult learning. Six units were designed to foster didactic, affective, and psychomotor learning specific to bullying and lateral violence and their prevention. Each unit consisted of formal lecture content, practice exercises, and reflection. OUTCOMES: This quality improvement project was well received by participants; a unit-based action plan resulted. Project materials are being reworked and new evidence integrated for deployment across the department. CONCLUSIONS: This initiative has demonstrated the necessary properties and is appropriate for adoption by other nursing units.

Telemedicine and Health Equity During COVID-19 in Pediatric Gastroenterology.

INTRODUCTION: Telehealth (TH) services rapidly expanded during the COVID-19 pandemic. This rapid deployment precluded the opportunity for initial planning of implementation strategies. The purpose of the quality improvement project was to understand the needs of nurse practitioners and examine TH procedures and interventions designed to promote high-quality, equitable health care for pediatric patients with gastrointestinal concerns. METHOD: The Plan-Do-Study-Act model was used. Survey data from providers and families were collected and analyzed. They were further illuminated through iterative dialog across the research team to determine the quality and efficiency of TH. RESULTS: A toolkit of strategies for promoting the quality and efficiency of TH was created according to the three domains of health equity: availability, accessibility, and acceptability. DISCUSSION: TH will be used in the postpandemic era. Institutions need to implement evidence-based strategies that ensure health equity across TH platforms to ensure excellent patient care.

A Genetics Learning Program for Nurses Caring for Children Treated With Ex Vivo Autologous Gene Therapy.

As our growing knowledge of genetics and genomics continues to inform, change, and customize health care, an understanding of genetics and genomics is now central to up-to-date and proficient nursing practice. There is a growing need for relevant nursing educational programs that aid practicing nurses in securing genetics/genomics knowledge and an understanding of gene therapy. This article describes a day-long, evidence-based, hands-on genetics learning program developed specifically for practicing nurses caring for children enrolled in ex vivo gene therapy clinical trials. [J Contin Educ Nurs. 2019;50(5):218-227.].

Building Genetic Competence Through Partnerships and Interactive Models.

BACKGROUND: Nurses are increasingly using genetic-directed therapies in routine care, but evidence indicates that nurse educators lack knowledge about basic genetic concepts and related clinical implications. Educators are the key to preparing future nurses for effective practice in the genomic era, and creative approaches are needed for faculty development. METHOD: Nurse educators in academic and clinical settings partnered with science educators who use sophisticated DNA, RNA, and protein models to explore ways to teach abstract genetic concepts. RESULTS: Hands-on learning enabled the workshop participants to understand how transcription of gene mutations leads to the translation of defective proteins responsible for specific diseases. Participants found using the models helped clarified complex concepts that occur at the cellular level. CONCLUSION: Partnerships with science educators can address gaps in nurse educators' knowledge about genetics and introduce creative teaching strategies. [J Nurs Educ. 2016;55(5):300-303.].

Implementation of the pediatric early warning scoring system on a pediatric hematology/oncology unit.

Despite improved outcomes for pediatric Hematology/Oncology patients over the past 15-20 years, sepsis and other acute events continue to cause serious illness in these children. Implementing a pediatric early warning scoring tool (PEWS) with an associated multi-disciplinary action algorithm in a pediatric Hematology/Oncology unit helped to remove barriers that prevented timely referral of children who are clinically deteriorating and requiring immediate help, enhanced multi-disciplinary team communication, and has led to a more than 3-fold increase in days between codes on the Hematology/Oncology unit.